Girotra Priti, Singh Shailendra Kumar
Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar, 125001, India.
Pharm Res. 2016 Jul;33(7):1682-95. doi: 10.1007/s11095-016-1910-8. Epub 2016 Mar 22.
The present investigation aimed at brain targeting of sumatriptan succinate (SS) for its optimal therapeutic effect in migraine through nanoparticulate drug delivery system using poly (butyl cyanoacrylate) (PBCA) and bovine serum albumin linked with apolipoprotein E3 (BSA-ApoE).
The study involved formulation optimization of PBCA nanoparticles (NPs) using central composite design for achieving minimum particle size, maximum entrapment efficiency along with sustained drug release. SS incorporated in BSA-ApoE NPs (S-AA-NP) were prepared by desolvation technique and compared with SS loaded polysorbate 80 coated optimized PBCA NPs (FPopt) in terms of their brain uptake potential, upon oral administration in male Wistar rats. The NPs were characterized by FTIR, thermal, powder XRD and TEM analysis.
The in vivo studies of FPopt and S-AA-NP on male Wistar rats demonstrated a fairly high brain/plasma drug ratio of 9.45 and 12.67 respectively 2 h post oral drug administration. The behavioural studies on male Swiss albino mice affirmed the enhanced anti-migraine potential of S-AA-NP than FPopt (P < 0.001).
The results of this work, therefore, indicate that BSA-ApoE NPs are significantly better than polysorbate 80 coated PBCA NPs for brain targeting of SS (P < 0.05) and also offer an improved therapeutic strategy for migraine management.
本研究旨在通过使用聚氰基丙烯酸丁酯（PBCA）和与载脂蛋白E3连接的牛血清白蛋白（BSA-ApoE）的纳米颗粒药物递送系统，使琥珀酸舒马普坦（SS）实现脑靶向，以在偏头痛治疗中获得最佳疗效。
该研究采用中心复合设计对PBCA纳米颗粒（NPs）进行制剂优化，以实现最小粒径、最大包封率以及药物的持续释放。通过溶剂挥发法制备了载于BSA-ApoE NPs（S-AA-NP）中的SS，并在雄性Wistar大鼠口服给药后，就其脑摄取潜力与载SS的聚山梨酯80包衣优化PBCA NPs（FPopt）进行比较。通过傅里叶变换红外光谱（FTIR）、热分析、粉末X射线衍射（XRD）和透射电子显微镜（TEM）分析对NPs进行表征。
FPopt和S-AA-NP对雄性Wistar大鼠的体内研究表明，口服给药2小时后，脑/血浆药物比分别相当高，为9.45和12.67。对雄性瑞士白化小鼠的行为学研究证实，S-AA-NP的抗偏头痛潜力比FPopt增强（P < 0.001）。
因此，本研究结果表明，对于SS的脑靶向，BSA-ApoE NPs明显优于聚山梨酯80包衣的PBCA NPs（P < 0.05），并且还为偏头痛治疗提供了一种改进的治疗策略。
